RGD Reference Report - Ketorolac salt is a newly discovered DDX3 inhibitor to treat oral cancer. - Rat Genome Database

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Ketorolac salt is a newly discovered DDX3 inhibitor to treat oral cancer.

Authors: Samal, Sabindra K  Routray, Samapika  Veeramachaneni, Ganesh Kumar  Dash, Rupesh  Botlagunta, Mahendran 
Citation: Samal SK, etal., Sci Rep. 2015 Apr 28;5:9982. doi: 10.1038/srep09982.
RGD ID: 151356506
Pubmed: (View Article at PubMed) PMID:25918862
DOI: Full-text: DOI:10.1038/srep09982

DDX3 belongs to DEAD box RNA helicase family and is involved in the progression of several types of cancer. In this work, we employed a High Throughput Virtual screening approach to identify bioactive compounds against DDX3 from ZINC natural database. Ketorolac salt was selected based on its binding free energy less than or equals to -5 Kcal/mol with reference to existing synthetic DDX3 inhibitors and strong hydrogen bond interactions as similar to crystallized DDX3 protein (2I4I). The anti-cancer activity of Ketorolac salt against DDX3 was tested using oral squamous cell carcinoma (OSCC) cell lines. This compound significantly down regulated the expression of DDX3 in human OSCC line (H357) and the half maximal growth inhibitory concentration (IC50) of Ketorolac salt in H357 cell line is 2.6 µM. Ketorolac salt also inhibited the ATP hydrolysis by directly interacting with DDX3. More importantly, we observed decreased number of neoplastic tongue lesions and reduced lesion severity in Ketorolac salt treated groups in a carcinogen induced tongue tumor mouse model. Taken together, our result demonstrates that Ketorolac salt is a newly discovered bioactive compound against DDX3 and this compound can be used as an ideal drug candidate to treat DDX3 associated oral cancer.

Disease Annotations    
tongue cancer  (IEP,ISO)

Gene-Chemical Interaction Annotations    
ketorolac  (EXP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Ddx3x  (DEAD-box helicase 3, X-linked)

Genes (Mus musculus)
Ddx3x  (DEAD box helicase 3, X-linked)

Genes (Homo sapiens)
DDX3X  (DEAD-box helicase 3 X-linked)

Additional Information